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Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT(1A) and 5-HT(1B) receptor agonists in the rat Parkinson model.

Munoz, Ana LU ; Carlsson, Thomas LU ; Tronci, Elisabetta LU ; Kirik, Deniz LU ; Björklund, Anders LU and Carta, Manolo LU (2009) In Experimental Neurology 219(1). p.298-307
Abstract
5-HT(1) receptor agonists have been shown to reduce abnormal involuntary movements (AIMs) in the rat and monkey models of l-DOPA-induced dyskinesia. Different mechanisms have been proposed to underlie this effect. Activation of pre-synaptic 5-HT(1) receptors has been suggested to inhibit dysregulated release of dopamine from the serotonin terminals, and thus, abnormal activation of striatal dopamine receptors. Activation of post-synaptic 5-HT(1) receptors expressed in non-serotonergic neurons in different brain areas, by contrast, has been shown to result in decreased glutamate and GABA release, which may also contribute to the antidyskinetic effect. To unveil the relative contribution of these mechanisms, we have investigated the effect... (More)
5-HT(1) receptor agonists have been shown to reduce abnormal involuntary movements (AIMs) in the rat and monkey models of l-DOPA-induced dyskinesia. Different mechanisms have been proposed to underlie this effect. Activation of pre-synaptic 5-HT(1) receptors has been suggested to inhibit dysregulated release of dopamine from the serotonin terminals, and thus, abnormal activation of striatal dopamine receptors. Activation of post-synaptic 5-HT(1) receptors expressed in non-serotonergic neurons in different brain areas, by contrast, has been shown to result in decreased glutamate and GABA release, which may also contribute to the antidyskinetic effect. To unveil the relative contribution of these mechanisms, we have investigated the effect of increasing doses of 5-HT(1A) and 5-HT(1B) receptor agonists on AIMs induced by either l-DOPA or apomorphine. In contrast to l-DOPA-induced AIMs, which were dampened already at low doses of 5-HT(1) agonists, reduction of apomorphine-induced AIMs required higher doses. Removal of the serotonin innervation suppressed l-DOPA-induced AIMs, but neither affected apomorphine-induced AIMs nor the inhibiting effect of 5-HT(1) agonists on AIMs induced by the direct dopamine agonist, suggesting that such effect is independent on activation of pre-synaptic 5-HT(1) receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
219
issue
1
pages
298 - 307
publisher
Academic Press
external identifiers
  • wos:000269398600035
  • pmid:19500572
  • scopus:68549126759
ISSN
0014-4886
DOI
10.1016/j.expneurol.2009.05.033
language
English
LU publication?
yes
id
f660a928-3ca4-402b-9a20-e849495cbfdd (old id 1434444)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19500572?dopt=Abstract
date added to LUP
2009-07-02 15:17:59
date last changed
2017-11-05 03:33:03
@article{f660a928-3ca4-402b-9a20-e849495cbfdd,
  abstract     = {5-HT(1) receptor agonists have been shown to reduce abnormal involuntary movements (AIMs) in the rat and monkey models of l-DOPA-induced dyskinesia. Different mechanisms have been proposed to underlie this effect. Activation of pre-synaptic 5-HT(1) receptors has been suggested to inhibit dysregulated release of dopamine from the serotonin terminals, and thus, abnormal activation of striatal dopamine receptors. Activation of post-synaptic 5-HT(1) receptors expressed in non-serotonergic neurons in different brain areas, by contrast, has been shown to result in decreased glutamate and GABA release, which may also contribute to the antidyskinetic effect. To unveil the relative contribution of these mechanisms, we have investigated the effect of increasing doses of 5-HT(1A) and 5-HT(1B) receptor agonists on AIMs induced by either l-DOPA or apomorphine. In contrast to l-DOPA-induced AIMs, which were dampened already at low doses of 5-HT(1) agonists, reduction of apomorphine-induced AIMs required higher doses. Removal of the serotonin innervation suppressed l-DOPA-induced AIMs, but neither affected apomorphine-induced AIMs nor the inhibiting effect of 5-HT(1) agonists on AIMs induced by the direct dopamine agonist, suggesting that such effect is independent on activation of pre-synaptic 5-HT(1) receptors.},
  author       = {Munoz, Ana and Carlsson, Thomas and Tronci, Elisabetta and Kirik, Deniz and Björklund, Anders and Carta, Manolo},
  issn         = {0014-4886},
  language     = {eng},
  number       = {1},
  pages        = {298--307},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT(1A) and 5-HT(1B) receptor agonists in the rat Parkinson model.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2009.05.033},
  volume       = {219},
  year         = {2009},
}